Clear Cell Renal Cell CarcinomaPhase 1/2NCT01684397
Pazopanib Hydrochloride and Bevacizumab in Treating Patients With Previously Untreated Metastatic Kidney Cancer
A Phase 1/2 study testing Bevacizumab, Laboratory Biomarker Analysis and Pazopanib Hydrochloride in people with Clear Cell Renal Cell Carcinoma and Stage IV Renal Cell Cancer, run by Roswell Park Cancer Institute at 5 sites in United States.
Trial summary
This phase I/II trial studies the side effects and best dose of pazopanib hydrochloride and bevacizumab and to see how well they work in treating patients with previously untreated kidney cancer that has spread to other places in the body (metastatic). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer
- What is being tested?
- Bevacizumab, Laboratory Biomarker Analysis and Pazopanib Hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 5 sitesUnited States
- Study dates
- 21 Nov 2012to 20 Feb 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biopsy/pathology-proven clear cell renal cell carcinoma (CCRCC) with metastases
- Have an Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- Hemoglobin >= 10 gm/dL
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 100 x 10^9/L
- Total bilirubin =< upper limit of normal (ULN)
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- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< ULN
- International normalization ratio (INR) and activated partial thromboplastin time (aPTT) < 1.2 x ULN
- Serum creatinine < 1.5 mg/dL or if serum creatinine > 1.5 mg/dL then calculate creatinine clearance (CrCL) > 30 mL/min
- Urine protein to creatinine ratio =< 1 (if urine protein creatinine ratio is > 1, then a 24-hour urine total protein must be assessed; subjects will be ineligible if the 24-hour urine protein is found to be > 1 gm)
- Normal cardiac ejection fraction (> 50%) by multi gated acquisition scan (MUGA) or echocardiogram
- Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
- Ability to swallow and retain oral medication
- Subjects of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
Who cannot join
- Subjects with known brain metastases should be excluded from this clinical trial
- Prior VEGF targeted therapies for renal cell carcinoma (RCC) including adjuvant or neoadjuvant treatments; in phase 1 only, one prior therapy with high dose IL-2 or anti-programmed cell death (PD)-1 compound alone or in combination with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) targeting drug is allowed on the trial
- Subjects diagnosed with another cancer in the past 3 years; excluding basal cell carcinoma or squamous cell carcinoma, of skin which were completely cured by resection
- Concurrent use of another anti-cancer drug including an investigational anti-cancer agent
- Major surgery within 28 days prior to treatment or major surgery planned during the next 6 months
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic or psychiatric illness/social situations that would limit compliance with study requirements
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- History of any of the following cardio-vascular condition:
- Myocardial infarction (MI)
- Unstable angina
- Coronary artery bypass grafting (CABG)-unless patient had a negative stress test within 6 months of screening
- Coronary angioplasty or stenting
- Symptomatic peripheral arterial disease (PAD)
- History of symptomatic chronic congestive heart failure (CHF)
- History of cerebrovascular accidents including transient ischemic attacks (TIA)
- Corrected QT interval (QTc) > 480 msec
- Uncontrolled hypertension (systolic blood pressure [BP] > 150 mm Hg or diastolic BP of > 90 mm Hg); if the screening BP is elevated, adjustments in anti-hypertensives are permitted and a re-screening will be permitted for BP assessment with three consecutive values obtained 2 minutes apart; the 3 values have to be below 150/90 mm Hg for eligibility and can only be obtained after 2 days of the last change in anti-hypertensive medication; use of clonidine is not permissible for adjusting the BP during this period
- History of deep vein thrombosis (DVT) or pulmonary embolism (PE) in the past 6 months
- Subjects should not have packed red blood cells (PRBC) or platelet transfusion within 14 days of the screening
- Evidence of active bleeding or bleeding disorder
- Subjects currently on anti-coagulation therapy are not eligible
- Unable to discontinue the use of prohibited medications
- Pregnant or nursing female subjects
- Unwilling or unable to follow protocol requirements
- Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive study drug
- Received an investigational agent within 30 days prior to enrollment
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
Karamanos Cancer Institute
Detroit, Michigan, 482018
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
The University of Kansas Cancer Center
Westwood, Kansas, 66205
About this study
Official title: A Phase I/II Trial of Pazopanib Alternating With Bevacizumab in Treatment-Naive Metastatic Clear Cell Renal Cell Carcinoma Patients
This phase I/II trial studies the side effects and best dose of pazopanib hydrochloride and bevacizumab and to see how well they work in treating patients with previously untreated kidney cancer that has spread to other places in the body (metastatic). Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Pazopanib hydrochloride may also stop the growth of tumor cells by blocking blood flow to the tumor. Monoclonal antibodies, such as bevacizumab, can prevent tumor growth by blocking the ability of tumor cells to grow and spread. Giving pazopanib hydrochloride together with bevacizumab may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- I. To determine the safe phase II dose of this novel regimen. (Phase I)
- II. To determine the median progression free survival (PFS) from this novel regimen. (Phase II)
SECONDARY OBJECTIVES:
- To evaluate the safety and toxicity of the proposed regimen. (Phase I)
- To evaluate the response rate. (Phase I)
- To evaluate the pharmacokinetics of pazopanib (pazopanib hydrochloride). (Phase I)
- To evaluate the vascular endothelial growth factor (VEGF) levels and myeloid derived suppressor cell (MDSC) levels at various time points and correlate with response. (Phase I)
- To evaluate the safety and toxicity of this new regimen. (Phase II)
- To evaluate the VEGF levels, interleukin (IL)-8 levels and MDSC levels at various time points and correlate with outcome. (Phase II)
- To evaluate the PFS rate at 12 months. (Phase II)
- To evaluate overall survival. (Phase II)
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive pazopanib hydrochloride orally (PO) on days 1-28, and bevacizumab intravenously (IV) over 30-90 minutes on days 36 and 50. Courses repeat every 70 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and Phase II patients are followed up by telephone every 12 months
- Being tested
- Bevacizumab, Laboratory Biomarker Analysis, Pazopanib Hydrochloride, Pharmacological Study
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabBiological
Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
Pazopanib HydrochlorideDrug
Also called GW786034B, Votrient
Given PO
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pazopanib hydrochloride and bevacizumab) | Experimental | Patients receive pazopanib hydrochloride PO on days 1-28 and bevacizumab IV over 30-90 minutes on days 36 and 50. Courses repeat every 70 days in the absence of disease progression or unacceptable toxicity. Receives: Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Drug: Pazopanib Hydrochloride; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median PFS (Phase II)
Distributions of continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.
Measured: Up to 30 days post-treatment
Optimal phase II dose, defined as the largest dose level at which less than 2 out of the 6 patients experienced dose-limiting toxicity, graded according to Common Terminology Criteria for Adverse Events version 4.0 (Phase I)
The frequency of toxicities will be tabulated for the dose estimated to be the maximum-tolerated dose.
Measured: Up to 140 days
Secondary outcomes (4)
Incidence of grade 3 or higher toxicities, graded according to CTCAE version 4.0
Categorical variables will be summarized in contingency tables, with associations of interest assessed using Fisher's exact test. The frequency of toxicities will be tabulated by grade across all dose levels and courses.
Measured: Up to 30 days post-treatment
Overall survival (Phase II)
Will be obtained using Kaplan-Meier and Proportional Hazards methods.
Measured: From the date of study enrollment to the date of death from any cause, assessed up to 30 days post-treatment
PFS rate at 12 months (Phase II)
Distributions of continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.
Measured: At 12 months
Response rate according to RECIST 1.1 (Phase I)
Measured: Up to 30 days post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2012 (estimated)
- Study start21 Nov 2012
- Primary completion20 Feb 2027 (estimated)
- Study completion20 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clear Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Roswell Park Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Saby George, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01684397
- Sponsor's protocol ID
- I 191711
- Other IDs
- NCI-2012-01247, 13-069, I 191711
- Status last verified
- Nov 2026
- First submitted
- 24 Aug 2012
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
George S, Vaishampayan U, Hutson A, Groman A, Pili R, Green K, Herbst L, Kallicharan-Smith R, DiRaddo AM, Farrell E, Gopalakrishnan D, Heath E, Wulff E, Kilari D, Appleman L, Parikh R. Pazopanib alternating with bevacizumab in patients with metastatic clear-cell renal cell carcinoma naive to treatment: a multicentre, single-arm, phase 1/2 trial. Lancet Oncol. 2026 Oct 27:S1470-2045(26)00394-3. doi: 10.1016/S1470-2045(26)00394-3. Online ahead of print.
PubMed 42945979
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Pazopanib Alternating With Bevacizumab in Treatment-Naive Metastatic Clear Cell Renal Cell Carcinoma Patients
- ClinicalTrials.gov ID
- NCT01684397
- Acronym / sponsor ID
- I 191711
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 21 Nov 2012 (actual)
- Primary completion
- 20 Feb 2027 (estimated)
- Study completion
- 20 Feb 2027 (estimated)
- First posted
- 13 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I/II trial studies the side effects and best dose of pazopanib hydrochloride and bevacizumab and to see how well they work in treating patients with previously untreated kidney cancer that has spread to other places in the body (metastatic). Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Pazopanib hydrochloride may also stop the growth of tumor cells by blocking blood flow to the tumor. Monoclonal antibodies, such as bevacizumab, can prevent tumor growth by blocking the ability of tumor cells to grow and spread. Giving pazopanib hydrochloride together with bevacizumab may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- I. To determine the safe phase II dose of this novel regimen. (Phase I)
- II. To determine the median progression free survival (PFS) from this novel regimen. (Phase II)
SECONDARY OBJECTIVES:
- To evaluate the safety and toxicity of the proposed regimen. (Phase I)
- To evaluate the response rate. (Phase I)
- To evaluate the pharmacokinetics of pazopanib (pazopanib hydrochloride). (Phase I)
- To evaluate the vascular endothelial growth factor (VEGF) levels and myeloid derived suppressor cell (MDSC) levels at various time points and correlate with response. (Phase I)
- To evaluate the safety and toxicity of this new regimen. (Phase II)
- To evaluate the VEGF levels, interleukin (IL)-8 levels and MDSC levels at various time points and correlate with outcome. (Phase II)
- To evaluate the PFS rate at 12 months. (Phase II)
- To evaluate overall survival. (Phase II)
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive pazopanib hydrochloride orally (PO) on days 1-28, and bevacizumab intravenously (IV) over 30-90 minutes on days 36 and 50. Courses repeat every 70 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and Phase II patients are followed up by telephone every 12 months
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (pazopanib hydrochloride and bevacizumab) | Experimental | Biological: Bevacizumab, Other: Laboratory Biomarker Analysis, Drug: Pazopanib Hydrochloride, Other: Pharmacological StudyPatients receive pazopanib hydrochloride PO on days 1-28 and bevacizumab IV over 30-90 minutes on days 36 and 50. Courses repeat every 70 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Biopsy/pathology-proven clear cell renal cell carcinoma (CCRCC) with metastases
- Have an Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- Hemoglobin >= 10 gm/dL
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 100 x 10^9/L
Key exclusion criteria (25 listed)
- Subjects with known brain metastases should be excluded from this clinical trial
- Prior VEGF targeted therapies for renal cell carcinoma (RCC) including adjuvant or neoadjuvant treatments; in phase 1 only, one prior therapy with high dose IL-2 or anti-programmed cell death (PD)-1 compound alone or in combination with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) targeting drug is allowed on the trial
- Subjects diagnosed with another cancer in the past 3 years; excluding basal cell carcinoma or squamous cell carcinoma, of skin which were completely cured by resection
- Concurrent use of another anti-cancer drug including an investigational anti-cancer agent
- Major surgery within 28 days prior to treatment or major surgery planned during the next 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, AvastinGiven IV | Biological | Treatment (pazopanib hydrochloride and bevacizumab) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (pazopanib hydrochloride and bevacizumab) |
| Pazopanib HydrochlorideAlso: GW786034B, VotrientGiven PO | Drug | Treatment (pazopanib hydrochloride and bevacizumab) |
| Pharmacological StudyCorrelative studies | Other | Treatment (pazopanib hydrochloride and bevacizumab) |
Primary outcome
Median PFS (Phase II)
Time frame: Up to 30 days post-treatment
Distributions of continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.
Optimal phase II dose, defined as the largest dose level at which less than 2 out of the 6 patients experienced dose-limiting toxicity, graded according to Common Terminology Criteria for Adverse Events version 4.0 (Phase I)
Time frame: Up to 140 days
The frequency of toxicities will be tabulated for the dose estimated to be the maximum-tolerated dose.
4 secondary outcomes
Incidence of grade 3 or higher toxicities, graded according to CTCAE version 4.0
Time frame: Up to 30 days post-treatment
Overall survival (Phase II)
Time frame: From the date of study enrollment to the date of death from any cause, assessed up to 30 days post-treatment
PFS rate at 12 months (Phase II)
Time frame: At 12 months
Response rate according to RECIST 1.1 (Phase I)
Time frame: Up to 30 days post-treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Derived from this study: PubMed 42945979George S, Vaishampayan U, Hutson A, Groman A, Pili R, Green K, Herbst L, Kallicharan-Smith R, DiRaddo AM, Farrell E, Gopalakrishnan D, Heath E, Wulff E, Kilari D, Appleman L, Parikh R. Pazopanib alternating with bevacizumab in patients with metastatic clear-cell renal cell carcinoma naive to treatment: a multicentre, single-arm, phase 1/2 trial. Lancet Oncol. 2026 Oct 27:S1470-2045(26)00394-3. doi: 10.1016/S1470-2045(26)00394-3. Online ahead of print.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Saby George principal investigator
Roswell Park Cancer Institute
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bevacizumab, Laboratory Biomarker Analysis and Pazopanib Hydrochloride in people with Clear Cell Renal Cell Carcinoma and Stage IV Renal Cell Cancer, run by Roswell Park Cancer Institute at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median PFS (Phase II) (time frame: Up to 30 days post-treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01684397, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.